Drug Design, Development and Therapy

The Correlation Between Neoadjuvant Chemotherapy for Ovarian Cancer and the Analgesic Effects of Remifentanil a Prospective Cohort Study

Neoadjuvant chemotherapy (NACT) is a key therapy for ovarian cancer that reduces tumor burden but injures normal tissues, necessitating meticulous anesthesia management. However, the pharmacokinetics and pharmacodynamics of remifentanil, a commonly used anesthetic analgesic, in this context remain inadequately studied, and relevant research in this patient population remains insufficient. This prospective observational cohort study aimed to evaluate the effect of preoperative NACT on intraoperative remifentanil requirements in ovarian cancer patients and assess perioperative outcomes to guide its rational clinical use. Seventy ovarian cancer patients undergoing surgery were divided into NACT (3 to 4 cycles of paclitaxel + carboplatin) and Non-NACT groups; 64 completed the study. The plasma concentration of remifentanil was titrated to maintain the intraoperative Index of Consciousness 2 (IOC2) value between 35 and 45. The primary outcome was average intraoperative remifentanil consumption; secondary outcomes included intraoperative and postoperative hemodynamic indicators, usage of vasoactive drugs, incidence of adverse events, and postoperative recovery indicators. Compared with the Non-NACT group, the NACT group had significantly higher intraoperative remifentanil consumption [11.89 ± 2.02 vs. 9.40 ± 1.81 μg·kg Preoperative NACT increases ovarian cancer patients' sensitivity to intraoperative pain, leading to higher remifentanil consumption and more frequent concentration adjustments. Clinically, higher intraoperative analgesic doses are needed for adequate pain control in this population.

Focus on Trabectedin in Ovarian Cancer: What Do We Still Need to Know?

In the era of single and combination maintenance therapies as well as platinum and Poly (ADP-ribose) polymerase inhibitors (PARPi) resistance, the choice of subsequent treatments following first-line platinum-based chemotherapy in recurrent ovarian cancer (ROC) patients has become increasingly complex. Within the ovarian cancer treatment algorithm, particularly in the emerging context of PARPi resistance, the role of trabectedin, in combination with pegylated liposomal doxorubicin (PLD) still preserves its significance. This paper offers valuable insights into the multifaceted role and mechanism of action of trabectedin in ROC. The main results of clinical trials and studies involving trabectedin/PLD, along with hints of Breast Cancer genes (BRCA)-mutated and BRCAness phenotype cases, are critically discussed. Moreover, this review provides and contextualizes potential scenarios of administering trabectedin in combination with PLD in ROC, according to established guidelines and beyond.

Efficacy and Safety of Anlotinib in Overall and Disease-Specific Advanced Gynecological Cancer: A Real-World Study

Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting. Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1-14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%). In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.

Oxycodone vs the Combination of Fentanyl and Remifentanil for General Anesthesia in Laparoscopic Uterine Myomas Surgery: A Prospective, Randomized, Controlled Study

This study evaluated whether oxycodone alone could substitute for fentanyl combined with remifentanil for general anesthesia in laparoscopic uterine myoma surgery. 90 adult female patients were randomized into three groups: oxycodone 0.35 mg/kg (Group A), oxycodone 0.30 mg/kg (Group B), or fentanyl 5 μg/kg (Group C) for induction. Anesthesia was maintained with propofol plus saline (Groups A/B) or remifentanil (Group C). Primary outcomes included Numerical Rating Scale (NRS) pain scores in the Post-Anesthesia Care Unit (PACU). Secondary outcomes were intubation reaction, vital signs, extubation/PACU times, Ramsey Sedation Scores (RSS) in PACU, NRS pain scores and adverse events within 48 hours postoperatively. Intubation reactions were rare (one case each in Groups B/C, none in Group A). Group B had significantly lower PACU NRS scores than Group C (0.6 ± 0.7 vs 1.3 ± 1.4, P = 0.011), while Group A showed a nonsignificant trend (0.8 ± 0.9 vs 1.3 ± 1.4, P = 0.051). RSS scores, extubation/PACU times, and 48-hour NRS scores were comparable. However, oxycodone groups had longer postoperative evacuation times than fentanyl group (Group A vs Group C: 20.0 ± 7.3 hours vs 16.5 ± 5.1 hours, P=0.038; Group B vs Group C: 20.3 ± 8.2 hours vs 16.5 ± 5.1 hours, P=0.034). Oxycodone alone provides superior early postoperative analgesia compared to fentanyl-remifentanil in laparoscopic myoma surgery but may delay bowel recovery.

Exploration of the Effect and Potential Mechanism of Echinacoside Against Endometrial Cancer Based on Network Pharmacology and in vitro Experimental Verification

Endometrial cancer (EC) is one of the most common gynecological malignancies, especially in postmenopausal women. Echinacoside (ECH) is a major natural bioactive ingredient derived from Cistanches Herba and Echinacea that has a variety of pharmacological effects. However, the efficacy and the mechanism of ECH against EC have not been elucidated yet. A compound-target-disease network was constructed to explore the potential targets and mechanism of ECH against EC. Molecular docking and in vitro experiments further verified the effect of ECH against EC. The potential targets of ECH against EC were retrieved from multiple public databases. Then, the protein-protein interaction (PPI) network was constructed to screen hub targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to discover the potential mechanism. Molecular docking was utilized to verify the binding affinity between hub targets and ECH. Finally, in vitro experiments were conducted to demonstrate the anti-EC effect of ECH. A total of 110 genes were identified as potential targets of ECH against EC. The GO enrichment analysis found that targets were primarily related to oxygen species, apoptosis, and other physiological processes. KEGG pathway analysis showed that PI3K/Akt signaling pathways might play an important role in ECH against EC. Molecular docking indicated that ECH had a significant binding ability with the EGFR, AKT1, ESR1, CASP3, HSP90AA1and MMP9 targets. Results from in vitro experiments revealed that ECH induced apoptosis of Ishikawa and HEC-1-B cells by promoting the arrest of the G2M phase, increasing ROS levels, and decreasing mitochondrial membrane potential (MMP) levels. Furthermore, treatment of ECH significantly reduced the expression levels of PI3K and p-AKT, and the combination of the PI3K inhibitor (LY294002) further enhanced the effects of ECH against EC. The findings suggested that ECH exerted an inhibitory effect on EC cells by inhibiting the PI3K/AKT pathway. Based on network pharmacology, molecular docking technology and in vitro experiments, we comprehensively clarified the anti-EC efficacy of ECH through multiple targets and signal pathways. Furthermore, we provided a novel idea of Traditional Chinese medicine (TCM) against EC.

A Retrospective Observational Study of Anlotinib in Patients with Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

Anlotinib, an oral small-molecular tyrosine kinase inhibitor (TKI) on tumor angiogenesis and growth, has a wide spectrum of inhibitory effects on targets such as vascular endothelial growth factor receptors 2/3 (VEGFR2/3), etc. The efficacy and safety of anlotinib in the treatment of platinum-resistant or platinum-refractory ovarian cancer were evaluated. Patients with platinum-resistant or platinum-refractory ovarian cancer that treated with anlotinib in the Affiliated Cancer Hospital of Zhengzhou University from May 2018 to March 2020 were included. Medical records were reviewed in terms of objective response, survival outcomes, and safety. A total of 38 patients were analyzed. The median progression-free survival and the median overall survival were 7.7 months (95% CI: 6.7-8.7) and 16.5 months (95% CI: 13.3-19.7), respectively. About 17 patients received anlotinib monotherapy, and the median progression-free survival was 7.7 months (95% CI: 6.3-9.1). A total of 19 cases received anlotinib plus chemotherapy with a median progression-free survival of 8.0 months (95% CI: 4.8-11.2). A total of 2 cases received anlotinib plus anti-PD-1 antibody pembrolizumab, and 1 case had partial response, the other progressive disease. The objective response rate was 42.1% while the disease control rate was 86.8%. A total of 5 patients experienced dose reduction from 12 mg to 10 mg because of adverse effects. The most common adverse effects were hypertension (31.6%), fatigue (28.9%), anorexia (26.3%) and hand-foot syndrome (23.7%). No treatment-related deaths were recorded. Anlotinib produced moderate improvements in progression-free survival and overall survival in patients with platinum-resistant or platinum-refractory ovarian cancer. It indicates that anlotinib maybe a new treatment option for patients with platinum-resistant or platinum-refractory ovarian cancer.

<p>Anti-Tumor Xanthones from <em>Garcinia nujiangensis</em> Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells</p>

Ovarian cancer (OC) is a serious public health concern in the world. It is important to develop novel drugs to inhibit OC. This study investigated the isolation, elucidation, efficiency, molecular docking, and pharmaceutical mechanisms of xanthones isolated from Xanthones were isolated, and purified by different chromatography, including silica gel, reversed-phase silica gel (ODS-C Bioassay-guided fractionation of the fruits of In conclusion, isojacareubin (

<p>Suppression of c-Met-Overexpressing Tumors by a Novel c-Met/CD3 Bispecific Antibody</p>

Overexpression of c-Met, or hepatocyte growth factor (HGF) receptor, is commonly observed in tumor biopsies and often associated with poor patient survival, which makes HGF/c-Met pathway an attractive molecular target for cancer therapy. A number of antibody-based therapeutic strategies have been explored to block c-Met or HGF in cancers; however, clinical efficacy has been very limited, indicating that blockade of c-Met signal alone is not sufficient. Thus, an alternative approach is to develop an immunotherapy strategy for c-Met-overexpressing cancers. c-Met/CD3 bispecific antibody (BsAb) could bridge CD3-positive T lymphocytes and tumor cells to result in potent tumor cell killing. A bispecific antibody, BS001, which binds both c-Met and CD3, was generated using a novel BsAb platform. Western blotting and T cells-mediated killing assays were utilized to evaluate the BsAb's effects on cell proliferation, survival and signal transduction in tumor cells. Subcutaneous tumor mouse models were used to analyze the in vivo anti-tumor effects of the bispecific antibody and its combination therapy with PD-L1 antibody. BS001 showed potent T-cell mediated tumor cells killing in vitro. Furthermore, BS001 inhibited phosphorylation of c-Met and downstream signal transduction in tumor cells. In A549 lung cancer xenograft model, BS001 inhibited tumor growth and increased the proportion of activated CD56 c-Met/CD3 bispecific antibody BS001 exhibited potent anti-tumor activities in vitro and in vivo, which was achieved through two distinguished mechanisms: through antibody-mediated tumor cell killing by T cells and through inhibition of c-Met signal transduction.

<p>Combination Treatment of Cervical Cancer Using Folate-Decorated, pH-Sensitive, Carboplatin and Paclitaxel Co-Loaded Lipid-Polymer Hybrid Nanoparticles</p>

Cervical cancer is one of the most common causes of death among women globally. Combinations of cisplatin, paclitaxel, bevacizumab, carboplatin, topotecan, and gemcitabine are recommended as first-line therapies. This study focuses on the development of folate-decorated, pH-sensitive lipid-polymer hybrid nanoparticles (LPNs). Loading carboplatin (CBP) and paclitaxel (PTX), LPNs were expected to combine the therapeutic effects of CBP and PTX, thus show synergistic ability on cervical cancer. FA-CBP/PTX-LPNs showed the sizes of 169.9 ± 5.6 nm, with a narrow size distribution of 0.151 ± 0.023. FA-CBP/PTX-LPNs exhibited pH-responsive drug release, high cellular uptake efficiency (66.7 ± 3.1%), and prominent cell inhibition capacity (23 ± 1.1%). In vivo tumor distribution and tumor inhibition efficiency of FA-CBP/PTX-LPNs was the highest, with no obvious body weight lost. High tumor distribution and remarkable antitumor efficiency obtained using in vitro as well as in vivo models further proved the FA-CBP/PTX-LPNs is a promising tool for cervical cancer therapy.

Molecular Pharmacological Interventions for Endometrial Cancer: A Comprehensive Review

Endometrial cancer, a common malignancy of the female reproductive system, has a rising incidence and complex clinical management due to its diverse molecular subtypes. This review examines the molecular mechanisms underlying EC, particularly the roles of the Bcl-2 family in apoptosis regulation and estrogen receptor signaling in tumor progression. We explore pharmacological interventions targeting these pathways, including BH3 mimetics and selective estrogen receptor modulators, which show promise but face challenges such as resistance and adverse effects. Additionally, we highlight the potential of natural compounds like curcumin, paclitaxel, and Ganoderma lucidum polysaccharides as adjunctive therapies, demonstrating efficacy in preclinical studies and early-phase clinical trials. This review aims to provide insights into the development of personalized therapeutic strategies for EC and to identify opportunities for optimizing clinical outcomes in future treatments.

Mechanism of Tetrandrine Against Endometrial Cancer Based on Network Pharmacology

Endometrial cancer (EC) is one of the most common gynaecological malignancies, and its incidence has been rising over the past decade. Tetrandrine, a bisbenzylisoquinoline alkaloid, has been isolated from a vine used in traditional Chinese medicine, This research was designed to predict the molecular mechanisms of tetrandrine against EC based on network pharmacology and to further verify these predictions by in vitro experiments. The potential therapeutic targets of tetrandrine against EC were predicted by using public databases. Afterwards, the protein-protein interaction (PPI) network of the common targets was constructed, and the key gene targets were obtained. Biological function and pathway enrichment analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Furthermore, molecular docking and in vitro experiments were carried out to verify the predictions. The cell counting kit‑8 (CCK‑8) assay, Hoechst 33258 staining, flow cytometry analysis, qRT-PCR, Western blot analysis and an immunofluorescence assay were performed. Our findings identified 111 potential therapeutic targets of tetrandrine against EC. We obtained 7 key gene targets from the PPI network analysis. Furthermore, GO enrichment analysis indicated that these targets were mainly associated with metabolic processes, responses to stimulus, and biological regulation. The KEGG pathway analysis showed that the common targets were mainly distributed in the PI3K/Akt signalling pathway. A potential interaction of tetrandrine with Akt1 was revealed by molecular docking. In addition, in vitro experiments showed that tetrandrine significantly inhibited cell proliferation and induced apoptosis in Ishikawa and HEC-1-B cells in dose- and time-dependent manners. The results also revealed that tetrandrine can downregulate the expression of Bcl-2 and upregulate the expression of Bax at the mRNA level. The mRNA levels of Akt were not significantly different in the various tetrandrine (0, 10 and 20µM) groups. However, Western blot analysis demonstrated that the protein expression ratios of p-Akt/Akt decreased at the protein level. The results were further confirmed by immunofluorescence assays. Based on bioinformatic analysis and experimental verification, our findings demonstrated that tetrandrine exerted tumour-suppressive effects on EC by regulating the PI3K/Akt signalling pathway.

OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo

OSU-03012 is a celecoxib derivative lacking cyclooxygenase-2 inhibitory activity and a potent PDK1 inhibitor which has been shown to inhibit tumor growth in various ways. However, the role of OSU-03012 in endometrial carcinoma (EC) in which the PI3K/Akt signaling pathway highly activated has not been studied. Here, we determined the potency of OSU-03012 in suppressing EC progression in vitro and in vivo, and studied the underlined mechanisms. The human EC Ishikawa and HEC-1A cells were used as the in vitro models. CCK8 assay and flow cytometry were conducted to evaluate cell proliferation, cell cycle progression, and apoptosis. The metastatic ability was evaluated using the transwell migration assay. The Ishikawa xenograft tumor model was used to study the inhibitory effects of OSU-03012 on EC growth in vivo. Western blot analysis was performed to evaluate expressions of the cell cycle and apoptosis associated proteins. OSU-03012 could inhibit the progression of EC both in vitro and in vivo by disrupting Akt signaling. It reduced the metastatic ability of EC, led to G2/M cell cycle arrest and induced apoptosis via the mitochondrial apoptosis pathway. Our data indicated that OSU-03012 could inhibit the progression of EC in vitro and in vivo. It can potentially be used as the targeted drug for the treatment of EC by inhibiting Akt signaling.

Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy

Genomic profiles relating to H101 treatment-induced alterations are yet to be achieved. Here, we evaluated the impact of H101 via exome-sequencing approaches aiming to probe for potential biomarkers that are actionable in the treatment of persistent/recurrent/metastatic (P/R/M) cervical cancer. Whole exome sequencing (WES) was performd on paired pre- and post-H101 samples from 17 P/R/M cervical cancer patients who received serial intra-tumor injections of H101. Somatic mutations, including high-frequency mutations, microsatellite instability (MSI) status, tumor mutation burden (TMB), clonal evolution, and mutational signature were analyzed. The median follow-up time after the H101 treatment was 14 months. Complete response was achieved in 9 patients, 3 patients achieved partial response, and 2 patients had stable disease, resulting in an objective response rate (ORR) of 70.6% (95% CI: 46.4%-96.7%). WES analysis showed no difference in treatment-related mutation characteristics, including non-synonymous-SNVs and TMB status. Patients with lower TMB were correlated with improved H101 response rates ( We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.

RGD-Conjugated Resveratrol HSA Nanoparticles as a Novel Delivery System in Ovarian Cancer Therapy

To establish a novel delivery system of RGD-conjugated resveratrol human serum albumin (HAS) nanoparticles in ovarian cancer therapy. The nanoparticles system was characterized for physicochemical properties, the stability in the serum and in vitro release. The comparison between RVT injection, HSA-RVT NPs and RGD-HSA-RVT NPs regarding tissue distributions and pharmacokinetics was also carried out using mice as the animal models. The results showed that RGD-HSA-RVT NPs were characterized of small particle size about 128.2 nm and negative zeta potential about -21.42 mV, and drug controlled to release slowly on a biphasic pattern. Compared with control groups, RGD-HSA-RVT NPs showed the higher cellular uptake and cell inhibition rates. In vivo data showed that RGD-HSA-RVT NPs have good tumor enrichment characteristics and a significant difference in tumor inhibition, compared with the control group. RGD-conjugated resveratrol HSA nanoparticles are an ideal drug delivery system, which can play a role in the treatment of ovarian cancer.

<p>Discovery of a Novel Benzenesulfonamide Analogue That Inhibits Proliferation and Metastasis Against Ovarian Cancer OVCAR-8 Cells</p>

Ovarian cancer has been a salient public health concern in the world. It is necessary to develop novel antitumor drugs to treat ovarian cancer. This study investigated the synthesis, antiproliferation ability, antitumor mechanisms in vitro and in vivo of a novel benzenesulfonamide derivative. The novel benzenesulfonamide-1,2,3-triazole hybrid We discovered that the benzenesulfonamide hybrid In conclusion, benzenesulfonamide hybrid

Pentamidine Inhibits Ovarian Cancer Cell Proliferation and Migration by Maintaining Stability of PTEN in vitro

Pentamidine is an anti-protozoal cationic aromatic diamidine drug and has been reported to exhibit anticancer properties. We aimed to identify the effect of pentamidine on proliferation and migration of human ovarian cancer (OC) cell lines and the related mechanisms. HO8910 and Caov3 ovarian cancer cells were treated with pentamidine. MTS and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using wound healing and transwell assays. The protein levels of PTEN, phosphorylated Akt, Akt, N-cadherin, E-cadherin and snail were detected by Western blotting. Immunoprecipitation and Western blotting were used to detect ubiquitination levels of PTEN. Our findings revealed that pentamidine inhibited both proliferation and migration of OC cells. Further investigation found that pentamidine increased the protein expression of PTEN and reduced phosphorylation levels of AKT in OC cells. Pentamidine treatment modulated PTEN stability through the ubiquitin/proteasome pathway. In addition, pentamidine inhibited the expression of N-cadherin and snail, and increased E-cadherin expression in a dose-dependent manner. Pentamidine is involved in the maintenance of PTEN protein stability and suppresses proliferation and migration of OC cells.

Combination of Sodium Cantharidinate with Cisplatin Synergistically Hampers Growth of Cervical Cancer

Sodium cantharidinate (SC) has been broadly applied in lung cancer treatment in China, while its specific function in cervical cancer (CC), a great contributor to death of female reproductive system cancers, remains unclear. Our research evaluated the anti-tumor effects of SC in CC and the mechanism involved. First, cisplatin (DDP)-resistant Caski-1 and ME180 cell lines were developed and treated with SC. The effects of SC on CC cell growth were then evaluated. Subsequently, the genes targeted by SC were predicted via the bioinformatics website. The correlations between PTPN1 expression and tumor stage, lymph node metastasis and tumor differentiation were examined. We further conducted rescue experiments by overexpressing PTPN1 in CC cells, followed by SC and cisplatin treatments. The activation of the PI3K/AKT pathway in CC cells, and the effect of SC on the growth and drug resistance of Caski-1 cells in vivo were investigated. The sensitivity of Caski-1 and ME180 cells to DDP was increased after SC treatment, which also enhanced the inhibitory effect of DDP on the cell growth. By prediction, we found that SC could target PTPN1. Patients with high expression of PTPN1 had higher clinical stage, lymph node metastasis and lower tumor differentiation. SC inhibited PTPN1 expression. Overexpression of PTPN1 attenuated the effect of SC. Furthermore, PTPN1 activated the PI3K/AKT pathway. Moreover, SC treatment inhibited the growth and drug resistance of Caski-1 cells in vivo. SC promotes drug sensitivity of CC cells to DDP by targeting PTPN1, thereby impairing the PI3K/AKT pathway.

Emerging Therapeutic Strategies of Different Immunotherapy Approaches Combined with PD-1/PD-L1 Blockade in Cervical Cancer

Currently, therapeutic methods for advanced and recurrent cervical cancer patients are limited and unsatisfactory. Immunotherapy is a promising approach for cancer treatment. However, its investigation and application in cervical cancer remain slow. Although pembrolizumab is a remarkable milestone as the first anti-PD-1 mAb approved by the FDA for treating cervical cancer, it shows relatively low response rate. It is noticed that multiple novel immune checkpoints have emerged in recent years, such as CTLA-4, TIGIT, LAG-3, TIM-3, and A2AR. Accumulated studies have suggested that strategies combining the PD-1/PD-L1 inhibitors and different immunotherapies or biotherapies could enhance the antitumor efficacy in human cancers. In this review article, we provide an overview of anti-PD-1/PD-L1-based immunotherapy in cervical cancer treatment. We further summarize the developmental strategies of different immunotherapies or biotherapies combined with PD-1/PD-L1 blockade for treating cervical cancer. We also discuss how these new combined therapies increase the therapeutic benefit gained from experimental evidence in cervical cancer.

Landscape Analysis of Human Papillomavirus (HPV) Prophylactic Vaccine Clinical Trials in China Based on the NMPA Database

Human papillomavirus (HPV) vaccination is key to preventing cervical cancer, and increasing its coverage in China faces complex challenges. Comprehensive literature providing an overview of the current status of HPV vaccine clinical trials in China remains lacking. To address this gap, our study was the first to systematically analyze and summarize the characteristics of HPV prophylactic vaccines clinical trials in China over a decade, providing a reference for HPV vaccine research and development. We analyzed HPV prophylactic vaccine clinical trials registered on the Chinese National Medical Products Administration (NMPA) Registration and Information Disclosure Platform (http://www.chinadrugtrials.org.cn) from January 1, 2013, to December 31, 2024. Eighty registered trials were evaluated, of which 51 trials (63.75%) were ongoing, 27 were completed (33.75%) and 2 were terminated (2.50%). The top three vaccine types by proportion were nonavalent vaccines (38.75%, n=31), followed by bivalent (35.00%, n=28) and quadrivalent (12.50%, n=10) vaccines. Domestic enterprises sponsored most trials (81.25%, n=65). The leading research sites were located mainly in the eastern and western China. Only 31.25% (n=25) of the trials had a data monitoring safety committee, and 43.75% (n=35) had clinical trial insurance. Most trials were in Phase III, with a randomized, double-blind, parallel-group design, and most (82.5%, n=66) enrolled female participants. Domestic vs overseas enterprises differed significantly in terms of phase ( HPV vaccine clinical trials in China have made significant progress, with most at a crucial stage, featuring diverse vaccine types and high-quality designs. However, more efforts are needed to promote the development and approval of the HPV vaccine by increasing tertiary hospitals' qualifications for conducting clinical trials, establishing a government-led non-profit third-party quality control platform and increasing research and development investment to ensure insurance coverage.

Enhanced Accumulation of Cisplatin in Ovarian Cancer Cells from Combination with Wedelolactone and Resulting Inhibition of Multiple Epigenetic Drivers

Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin. Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780 Cisplatin and wedelolactone showed a dose-dependent growth inhibitory effect. RF value of wedelolactone was 1.1 in the case of A2780 These findings have shown that additive outcome of drug combination in A2780

<p>Regulations of miR-183-5p and Snail-Mediated Shikonin-Reduced Epithelial-Mesenchymal Transition in Cervical Cancer Cells</p>

Shikonin, the main ingredient of MTT, wound-healing, transwell assays and flow cytometry experiments were used to measure cell growth, migration, invasion, and cell cycle analysis. Western blot was used to examine protein levels of Snail, Vimentin and E-cadherin. The expression level of miR-183-5p was measured via qRT-PCR. The E-cadherin promoter activity was detected via Secrete-PairTM Dual Luminescence Assay Kit. The transient transfection experiments were used for silencing of E-cadherin and overexpression of Snail genes. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings. We showed that shikonin inhibited cell viability, migration and invasion, and induced cell cycle arrest in a dose-dependent manner in cervical cancer Hela and C33a cells. Mechanistically, we found that shikonin increased miR-183-5p expression and inhibited expression of transcription factor Snail protein. The mimics of miR-183-5p reduced, while the inhibitors of miR-183-5p reversed shikonin-inhibited Snail protein expression. In addition, shikonin decreased Vimentin, increased E-cadherin protein expressions and E-cadherin promoter activity, the latter was reversed in cells transfected with exogenous Snail overexpression vectors. Moreover, silencing of E-cadherin significantly abolished shikonin-inhibited cervical cancer cell growth. Similar findings were also observed in vivo using one xenograft mouse model. Our results show that shikonin inhibits EMT through inhibition of Snail and stimulation of miR-183-5p expressions, which resulted in induction of E-cadherin expression. Thus, blockade of EMT could be a novel mechanism underlying the anti-cervical cancer effects of shikonin.

A Retrospective Cohort Study Evaluates Clinical Value of Anlotinib in Persistent, Metastatic, or Recurrent Cervical Cancer After Failure of First-Line Therapy

Anlotinib is an oral anti-angiogenesis inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors, fibroblast growth factor receptors, etc., and its clinical value in cervical cancer is rarely reported. We designed a retrospective study to evaluate the efficacy and safety of anlotinib in patients with persistent, metastatic, or recurrent cervical cancer who have failed first-line therapy, and compare the efficacy of anlotinib with that of apatinib which targets only VEGFR2 and has shown efficacy in recent studies. Fifty-two patients with persistent, metastatic, or recurrent cervical cancer who failed first-line therapy and administrated anlotinib or apatinib as monotherapy or combination with chemo-, radio- or immunotherapy were included in this study. Among the 52 patients, 20 patients who received anlotinib from January 2019 to August 2020 were defined as anlotinib group, whereas 32 patients who received apatinib from our previous study were selected as apatinib group. The safety, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were reviewed and recorded. The ORR and DCR in patients receiving anlotinib were 25% and 80%, respectively. The median PFS and OS in anlotinib group were significantly longer than those in apatinib group, respectively (PFS: 5 months vs 3 months, p=0.015; OS: 10 months vs 5 months, p=0.008). Moreover, the patients treated with anlotinib had better survival with a significantly lower cumulative incidence of cancer-related death than those treated with apatinib (HR=0.31, 95% CI: 0.13-0.77, p=0.012). The most common adverse effects in the patients treated with anlotinib were hypertension (20%), fatigue (20%), and nausea (15%). No drug-related death occurred. Anlotinib showed beneficial efficacy and safety and can be a treatment option for patients with persistent, metastatic, or recurrent cervical cancer who have failed the first-line therapy.

Effects of Quercetin on the Efficacy of Various Chemotherapeutic Drugs in Cervical Cancer Cells

This study aimed to investigate the effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells. All drug experiments were performed in HeLa and SiHa cells. The cell viability was detected by Cell Counting Kit-8 assay, and cell proliferation was estimated by bromodeoxyuridine assay. CompuSyn software was utilized to calculate the combination index (CI) and evaluate the synergistic or antagonistic effect of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin on cell viability. Cell migration and invasion abilities were detected by transwell assays, and cell apoptosis was measured by flow cytometry. The expression levels of matrix metallopeptidase 2 (MMP2), ezrin, P-glycoprotein (P-Gp) and methyltransferase-like 3 (METTL3) protein treated with various drugs were analyzed by Western blotting. Quercetin inhibited the viability of HeLa and SiHa cells in a dose- and time-dependent manner. The CI values of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin were 1, >1 and >1, respectively. The effect of combination of quercetin and cisplatin on cell proliferation was stronger than their individual effects. Co-treatment group could inhibit more cell migration and invasion in contrast to single-drug group. Besides, quercetin combined with cisplatin group induced more cell apoptosis in contrast to single-drug group. The results of Western blotting showed that the expression levels of MMP2, ezrin, P-Gp and METTL3 in co-treatment group were lower than in cisplatin group, respectively. Quercetin and cisplatin had synergistic inhibitory effect on cervical cancer cells. Quercetin might enhance the antitumor effect of cisplatin via inhibiting proliferation, migration and invasion and elevating apoptosis through weakening MMP2, ezrin, METTL3 and P-Gp expression of cancer cells.

A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells

Metastasis causes approximately 90% of cancer-related deaths, including in cervical cancer patients. Uncontrolled cell proliferation, migration, and cancer stemness act as critical events in primary tumor growth and cancer metastasis progression in cervical cancer. Here, we investigated the anti-proliferative, anti-migration, and cancer stemness inhibition activity of N-phenyl pyrazoline derivatives against cervical cancer cells. The chalcone and phenylhydrazine were used to synthesize the N-phenyl pyrazoline 2/5 (P2 and P5). The MTT, colony formation, and wound healing assays were performed to evaluate the N-phenyl pyrazoline effect in HeLa cells. The N-phenyl pyrazoline's protein target was predicted using SwissTargetPrediction and AutoDock Vina software. The Western blotting assay was performed to evaluate the target proteins. The public dataset analysis was used to confirm the clinical relevance of target protein in cervical cancer patients. N-phenyl pyrazoline 2 and 5 were successfully synthesized. The N-phenyl pyrazolines 2 and 5 exhibit cytotoxic effect in HeLa cell line with 20.26 µM, 4.708 µM of IC N-phenyl pyrazoline 5 suppresses the cell viability, proliferation, migration, and cancer stem cell-like phenotype of cervical cancer cells via EGFR inhibition.

Efficacy and Prognostic Factors for Response to PD-1 Inhibitors in Advanced Cervical Carcinoma: A Retrospective Study

Programmed cell death protein 1 (PD-1) inhibitors have shown a therapeutic effect in the treatment of advanced cervical cancer in clinical trials. However, the clinical characteristics associated with response remain undetermined. This study aimed to evaluate the efficacy and prognostic factors of PD-1 inhibitors in patients with advanced cervical cancer in clinical practice. The study enrolled patients with recurrent or metastatic cervical cancer treated with PD-1 inhibitors at our center between March 2018 and November 2020. The primary outcomes were the objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. In addition, independent prognostic factors were identified by multivariate regression analysis. A total of 102 patients were included, and the ORR and disease control rate (DCR) were 51.0% and 66.7%, respectively. Median PFS was 11.0 months (95% CI, 1.7-20.4), while median OS was not achieved. Multivariate analysis indicated that factors associated with a better prognosis (ORR and PFS) included squamous cell carcinoma, a time to recurrence >6 months, and PD-1 plus chemotherapy and anti-angiogenic drugs ( PD-1 inhibitors demonstrated beneficial efficacy and safety in advanced cervical cancer, particularly for patients with squamous cell carcinoma, a time to recurrence >6 months, or PD-1 plus chemotherapy and anti-angiogenic drugs. Further studies are needed to confirm the long-term outcomes.

Effects of Different Doses of Butorphanol on Perioperative Analgesia, Recovery, and Immune Function in Patients Undergoing Cytoreductive Surgery for Ovarian Cancer: A Randomized Controlled Trial

To investigate the optimal dose of butorphanol for patient-controlled intravenous analgesia (PCIA) by evaluating its effects on perioperative pain control and immune function in patients undergoing ovarian cancer surgery. Patients undergoing ovarian cancer surgery between May 2023 and March 2025 were randomized into four PCIA groups: Group S (sufentanil 0.04 μg·kg VAS score at T3 was lower in group B3 than in S ( High-dose butorphanol PCIA effectively relieves postoperative pain and reduces time to early ambulation without affecting immune indicators within 48 h postoperatively.